Autologous hematopoietic stem cell transplantation in tandem with anti-CD30 CAR T-cell infusion in relapsed/refractory CD30<sup>+</sup> lymphoma.
Authors: Xiuxiu Yang, Peiling Zhang, Yang Cao, Jue Wang, Mi Zhou, Chunrui Li, Jianfeng Zhou, Liang Huang
Journal: Journal of Clinical Oncology (2022)

7532 Background: Long-term outcome is unfavorable for patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL) who are resistant to salvage chemotherapy, even followed by autologous stem cell transplantation (ASCT). Long-term survival is most likely achieved in patients who are sensitive to salvage therapy and have a complete response (CR) before ASCT, while outcome is poor in patients with residual disease. Although CD30-directed chimeric antigen receptor (CAR30) T-cell therapy induces high response rates in these patients, the duration of response is limited. Methods: We conducted an open-label, single-center and single-arm pilot study to explore the safety and efficacy of ASCT in tandem with CAR30 T-cell infusion in r/r CD30 + lymphoma (Chinese Clinical Trial Registry, number ChiCTR 2100053662). Patients will receive BEAM as preconditioning. HSCs are infused at day zero and followed by the infusion of 3rd generation CAR30 T cells in the next week. Between June 1, 2019 to May 1, 2021, 6 patients enrolled, including 5 with cHL and 1 with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL). The median age was 24 years. No patient had a prior history of ASCT. Three patients (50.0%) relapsed ≥ 2 times and 3 patients (50.0%) had primary refractory diseases. All had a Deauville score of 4 or 5, and 5 patients (83.3%) had a stable or progressive disease (SD/PD) to previous treatments at enrollment. Results: CD34 + cells were infused at day zero with a median dosage of 3.9 (IQR, 3.2-6.1) × 10 6 /kg and followed by the infusion of CAR30 T cells with a median dosage of 7.6 (IQR, 5.5-9.7 ) ×10 6 /kg at +2 to +6 days. Cytopenias represented the most commonly severe advers events (≥ grade 3). The engraftments of neutrophil or platelet occured at a median time of 13.5 (IQR,12.3-14.0 ) days or 11.5 (IQR, 11.0-12.8) days, respectively, suggesting rapid multilineage engraftments post-ASCT. Cytokine release syndrome (CRS) was observed in 5 (83.3%) patients, all of which were grade 1. No neurotoxicity or severe infection was observed. At month 3 after HSC infusion, all patients achieved objective responses, including 5 (83.3%) with a CR and 1 with a patial response (PR). With a median follow-up of 18.2 (range, 9.9-32.1) months, the median PFS and OS were not reached. At January 31, 2022, the data-cutoff date, all patients maintained their responses and remained alive without disease relapse or progression. Of note, responses were sustained in all 5 patients who had a SD/PD at enrollment. Conclusions: Our work demonstrates tandem administration of ASCT and CAR30 T-cell therapy was well-tolerated and highly active in r/r HL and ALCL, even in PET-positive or chemorefractory patients who were expected to have inferior outcome after ASCT, although further large-scale validation in prospective clinical trial is warranted. Clinical trial information: ChiCTR2100053662.